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Healthy blood cells of 115-year-old woman show hundreds of mutations

Published
Thursday 24 April 2014 Published Thu 24 Apr 2014

By Marie Ellis

In 2005, a 115-year old woman died and became the oldest person ever to donate her body to science. Now, researchers who analyzed the healthy blood cells in her body say they have identified over 400 genetic mutations, suggesting such lesions are mostly harmless in our bodies over a lifetime.

The researchers, led by Dr. Henne Holstege of VU University Medical Center in the Netherlands, publish their findings in the journal Genome Research.

They explain that genetic mutations are widely studied in the field of medicine - due to their links with diseases such as cancer - but very little is known about mutations in the bodies of healthy people.

Stem cells in our bone marrow are constantly dividing to create new blood cells, but the researchers note that the process of cell division introduces errors, and the dividing cells can acquire genetic mutations.

In patients with blood cancers, hundreds of mutations have been found; however, it has not been clear whether healthy white blood cells also contain mutations.

Study points to limits of human longevity

Pictured is the birth of hematopoietic stem cells (blue) in a mouse embryo's blood vessel. Image credit: Nancy Speck, Univ. of Pennsylvania School of Medicine

The woman did not have any symptoms of hematological illnesses, the researchers say, and add that an autopsy showed she "did not suffer from vascular or dementia-related pathology."

Results showed that there were over 400 somatic mutations - those that are not passed on to offspring and do not lead to disease - in the white blood cells that were not found in her brain.

The team explains that brain cells rarely experience cell division after birth.

The mutations they found were mostly in non-coding regions of the genome that have not previously been linked with disease, but they were in "mutation-prone" areas, such as "methylated cytosine DNA bases and solvent-accessible stretches of DNA."

Dr. Holstege explains that she and her team may have uncovered results that point at the limits of human longevity:

"To our great surprise we found that, at the time of her death, the peripheral blood was derived from only two active hematopoietic stem cells (in contrast to an estimated 1,300 simultaneously active stem cells), which were related to each other."

In addition to these findings, upon examining the length of the telomeres - protective repetitive sequences at the ends of chromosomes - the team found that the white blood cell telomeres were 17 times shorter than those in the brain.

Dr. Holstege says as a result of this finding, they "speculate that most hematopoietic stem cells may have died from 'stem cell exhaustion,' reaching the upper limit of stem cell divisions."

However, she adds that future studies need to investigate whether stem cell exhaustion is a likely cause of death at very old ages.

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